Effectiveness between 2.5% Povidone-Iodine Eye Drop and 1% Tetracycline Eye Ointment. Hamidah Ali and Retno Sutarti ABSTRACT

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1 THE COMPARISON OF THE EFFECTIVENESS BETWEEN 2.5% POVIDONE-IODINE EYE DROP AND 1% TETRACYCLINE EYE OINTMENT ON BACTERIAL OPHTHALMIA NEONATORUM PROPHYLAXIS Hamidah Ali and Retno Sutarti ABSTRACT Background: Ophthalmia neonatorum is an acute conjunctivitis in infant caused by bacterial gram positive, gram negative, herpes virus and HIV virus. The most frequent bacterial causes are perinatally-acquired gonococcus and chlamydia. Before prevention the cases demonstrated a high rate and after prevention the rate is decreased. Many preventive agents are used including 1% silver nitrate solution, 0.5% erythromycine eye ointment and 2.5% povidoneiodine eye drop (new application). Every country chooses and recommends those drugs differently as prophylaxis. Objective: To know the difference of the effectiveness between 2.5% povidone-iodine eye drop and 1% tetracycline eye ointment in newborn at Dr. Soetomo Hospital. Method: This study used experimental pre- and posttest design, i.e. comparing the effectiveness between 2.5% povidone-iodine eye drop and 1% tetracycline eye ointment. Population of study were 148 normal babies, divided into two groups: i.e., group one of 74 babies treated with 2.5% povidone-iodine eye drop and the second group comprised 74 babies with 1% tetracycline eye ointment. The data were collected and analyzed statistically with Chi-square test, Wilcoxon sign rank tests, Mann Whitney, McNemar and homogeneity test (p < 0.05 significantly). Result: the effectiveness of 2.5% povidone-iodine eye drop and 1% tetracycline eye ointment, both clinically and laboratory, were good. The differences were not significant. Chi - square test in clinical examinations showed that conjuctival hyperaemie had p= 1.000, conjunctival secretion had p= 0.202, Laboratory examinations revealed: polymorphonuclear cell p = 0.831, mononuclear cell p = and the decrease of bacteria = Conclusion: The effectiveness of 2.5% povidone-iodine eye drop and 1% tetracycline eye ointment is similar p > 0.05, thus 2.5% povidone-iodine can be considered as prophylaxis in newborn babies. Keywords: ophthalmia neonatorum, povidone-iodine, tetracycline INTRODUCTION Ophthalmia Neonatorum is an acute conjunctivitis in newborn babies caused by bacterial gram positive, gram negative and virus. The most frequent bacteria causing blindness of the newborn babies are gonococcus and the second was chlamydia (CAN 1992; Wilhelmus, 2001; Zhao Feng, 2001; Kua Sheree, 2000). In the United States many preventive agents of ophthalmia neonatorum are used, including silver nitrate 1% eye drop. The incidence was decreased drastically, from 100 per 1000 life-birth to 3 per 1000 life-birth. In 1983 The Infection Diseases and Immunization Committee of The Canadian Pediatrics Society recommended that the use of silver nitrate 1%, tetracycline hydrochloride 1 % eye ointment and erythromycine 0.5% eye oinment could be given to the newborn babies for ophthalmia neonatorum prevention. Department of Ophthalmology Airlangga University School of Medicine Dr Soetomo Teaching Hospital, Surabaya Nevertheless, Singapore Medical Journal reported that there was bacterial resistance of 1% tetracycline eye ointment, so that the effectiveness of 1% tetracycline was in doubt for prevention. In 1995 Isen Berg had accomplished his research in Kenya, comparing 2.5% povidone-iodine, silver nitrate 1% and erythromycines 0.5% ointment in 3,136 babies. The result was that povidone-iodine was more effective than 1% silver nitrate and 0.5% erythromycine, and that povidoneiodine had wider anti bacterial spectrum, more effective anti virus and non toxic preventive agent for conjunctivitis neonatorum (CMA Journal 1999, 2000, Ho KN 1996, Diamant 1999, Kua Sheree 2000) Many researches showed that erythromycine eye ointment, tetracycline eye oinment and silver nitrate were effective to prevent gonococcal conjunctivitis, but were not effective for chlamydia. The other researches stated that povidone-iodine was more effective for conjunctivitis neonatorum, besides being recommended as the prevention of other causes. Regarding its cost, povidone-iodine is cheaper than 1% tetracycline eye ointment. Owing to this condition, this research was conducted to find the differences of the effectiveness of Folia Medica Indonesiana 102

2 both agents; 1% tetracycline eye ointment and 2.5% povidone-iodine eye drop in newborn babies. The objective of this research was to find the differences between both two agents. If the effectiveness of 2.5% povidone-iodine is better, we will propose this agent as the substitution of standardized 1% tetracycline, but if they have the same effectiveness, povidone-iodine will be considered to be the alternative agent. MATERIAL AND METHOD The study used experimental pre- and posttest design, comparing the effectiveness between 2.5% povidoneiodine eye drop and 1% tetracycline eye oinment. This study was done in Dr. Soetomo Hospital Surabaya, from April to June According to James E. Higgins (1985), the right number of samples was 148. The samples were divided into two groups. The first group of 74 newborn babies was treated with 2.5% povidoneiodine eye drops, and the second group of 74 newborn babies was treated with 1% tetracycline eye ointment. Both agents were given to both eyes of the babies, one hour after being born. The research population was all normal newborn babies by normal birth. Inclusive Criteria: All newborn normal babies by normal at term birth with body weight > 2500 grams, Apgar Score 7-8, no hereditary differences, and their parents are participated to the research. Exclusive Criteria: underweight premature born babies with asphyxia and any hereditary differences. After both of eyes of the babies were given with 2.5% povidone-iodine eye drops or 1% tetracycline eye ointment, the eyes were cleaned with sterile cotton, while irrigation was not made. Before and after treatment the babies were clinically and laboratory tested, and analyzed for the side effects of the agents. The 2.5% povidone-iodine eye drop is Betadine 10% solution, 1 cc added by 4 cc distilled water in 5 cc disposable syringe. The excess were dropped out and done by the researcher herself. 1% tetracycline eye ointment was 1% Oxytetracycline of 3.5 gram tube, in which every gram had Oxytetracycline Hydrochoride 10.8 mg equal with Oxytetracycline 10 mg. To find the clinical response of both agents, after 24 hours, before leaving out the hospital, clinical and laboratory Gram staining test were done. Clinical tests were conjunctivitis hyperamia, conjunctive chemosis, conjunctive edema, conjunctive secretion, three grades for each: none, light and medium. Gram staining test was done on the conjunctive secret to identify: a. Cell PMN and MN b. < 5 / visual field or > 5 / visual field c. Bacterial : available or none d. If available : Bar or Coccus The treatment was regarded as effective when there was no more hyperaemia, conjunctive chemosis, secretion, less or no bacteria, PMN Cell and MN Cell and < 5 visual field. Data tabulation and analysis were conducted using chi square, homogenous Mann Whitney and McNemar tests with significance level of alpha = 0.05, so it was regarded as significant (S) if p < 0.05 and not significant (NS) if p > RESULT AND DISCUSSION Table 1. Homogeneity test between variables No Variables Povidone- Iodine Statist. Test P Sex (M : F) Anamnesis on Mother s : Fluor albus (+ : -) Antenatal Frequency 40 (54.1%) : 34 (45%) 16 (21.6%) : 58(78.4%) (47.3%):39 (52.73%) 25(33.8%) : 49(66.2%) X2 X 2 T test Body weight by birth T test APGAR menu Mann Whitney Folia Medica Indonesiana 103

3 Table 1 shows homogeneity among povidone-iodine and tetracycline groups. Variable of sex between boy babies and girl babies of the povidone-iodine group and group was not significantly different (p = 0.411). Variable of fluor albus on the babies' mothers during pregnancy in the antenatal visit, body weight was 3.053, ,16 for the povidon-iodine group and 3.053, ,88 for tetracycline group. So there was no significant difference (p = 0.053) between povidoniodine and tetracycline groups. Also there were no significant differences between the groups by Mann Whitney Test on the variables of number of visits (p = 0.441), birthweight (p = 0.998), and Apgar Score (p = 0.065). Apgar Score variable showed almost the same value 7-9 of povidone-iodine and tetracycline groups. This result figured out that each variable was homogenous for both groups. The goal of this homogenous test was to show bias selection and confusing effect of the variable between two groups were proportional and stable. The variables above had no differences between povidone-iodine and tetracycline groups. Clinical Test Distribution Table 2. Distribution in clinical test of edema palpebrae Before After Groups None Light Medium Total None Light Medium Total Povidone iodine 30 (40.5%) 44 (59.5%) 5 (6.8%) 69 (93.2%) 74 (100%0 Total 35 (23.6%) 113 (76.3%) 148 (100%) 148 (100 %) 148 (100%) Table 2 shows that the distribution on clinical test of edema palpebrae had the highest value in 44 babies (59.5%) with minor edema palpebrae in povidoneiodine. and 69 babies (93.2%) in tetracycline. The chisquare test showed p = before treatment. There were significant differences in edema palpebrae distribution before treatment between both two agents, while after treatment there were no edema palpebrae in babies in povidone-iodine and also from 74 babies (100%) in tetracycline group. The McNemar test for both agents had p = This was because the edema palpebrae in those newborn babies was not caused by the inflammation process, but caused by physiological process in the birth itself. Therefore, the edema palpebrae improvement change could not be used as the treatment effectivity parameter. Table 3. Distribution of clinical test on conjunctivitis hyperaemia Before After Group None Light Medium Total None Light Medium Total Povidone- iodine 9 (12.2%) 60 (81.1%) 5 (6.8%) 63 (85.1%) 11(14.9% 4 (5.4%) 62 (83.8%) 8 (10.8%) 63 (85.1%) 11 (14.9%) Total 13 (8.8%) 122 (82.4%) 8 (10.8%) 126 (58%) 22 (14.9%) 148 (100%) After treatment, it was shown that 11 babies (14.9%) had light hyperaemia in the povidone-iodine group, and 11 babies (14.9%) in the tetracycline group. Then Wilcoxon statistical test was done to each group before and after treatment. Both groups had p = In conclusion, both treatments resulted in significant decrease of conjunctivitis hyperaemia. The better healing of conjunctivitis hyperaemia in this study was a successful parameter of povidone-iodine and tetracycline treatment, as mentioned in the literature. Comparing the effectiveness of both agents by chisquare test after treatment (p = 1.000) and Mann Whitney test (p = 0.151), there was no significant difference between 2.5% povidone-iodine and 1% tetracycline treatment. Folia Medica Indonesiana 104

4 Table 4. Distribution of clinical test on the secret of conjunctivitis Before After Group None Light Medium Total None Light Medium Total Povidone-iodine 1 (5.4%) 65 (87.8%) 5(6.8%) 66 (89.2%) 6 (8.1 %) 2 (2.7%) 10 (13.5%) 59 (79.7%) 5 (6.8%) 60 (81.1%) 13 (17.6%) 1(1.4%) Total 14(9.5%) 124 (83.8%) 10 (13.5%) 148 (100%) 19 (12.8%) 19 (12.8%) 3 (2.0%) 148 (100%) The result of clinical test on secret of conjunctivity in Table 4 was that most of 65 babies (87.8%) had light conjunctivity in povidone-iodine group and 59 babies (79.7%) in tetracycline group before treatment. After treatment it was decreased to 6 babies (8.1%) in povidone-iodine group and 13 babies (17.68%) in tetracycline group. The Wilcoxon Statitic Test showed a better clinical healing of the secret of conjunctivity significantly, for each group, p = The chi-square test showed that p = for povidone-iodine group and tetracycline group before treatment, and p = after treatment (Mann Whitney Test, p = after treatment), so there was no significant difference in the effectiveness of both agents. Laboratory Test Distribution Table 5. Distribution of laboratory test on PMN Before After Group < 5 >5 Total < 5 > 5 Total Povidone-iodine 49 (66.2%) 25 (33.8%) 63 (85.1%) 11 (14.9%) 56 (75.7%) 18 (24.3%) 65 (87.8%) 9 (12.2%) Total 105 (70.9%) 43 (29.1%) 148 (100%) 128 (86.5%) 20 (13.5%) 148 (100%) The laboratory test showed that the number of polymorphonuclear (PMN) cells in Table 5 has the highest distribution number of PMN cell per visual field. In povidone-iodine group there were 49 babies (66.2%) with PMN cells <5, and 25 babies (33.3%) with PMN cells > 5 before treatment. After treatment there were 63 babies (85.1%) with PMN cells < 5 and 11 babies (14.9%) with PMN cells > 5, with the highest value 87.8%. Using McNemar test, we got p = In tetracycline group there were 56 babies (75.7%) with PMN cells <5 and 18 babies (24.3%) with PMN cells > 5 before treatment, and after treatment we got 65 babies (87.8%) with PMN cells < 5 and 9 babies (12.2%) with PMN cells > 5. Using McNemar test we got p = In povidone-iodine group as well as tetracycline group we got PMN significant cell decrease. Comparing both two groups by using chi-square test, we got p = before treatment and p = (Mann Whitney Test, p = 0.379) after treatment. It can be concluded that there were no significant difference between both groups, before and after treatment. It was apparent that PMN cell count per visual field can be used as bacterial infection parameter. Thus, the significance of reduced PMN count decrease indicated the effectiveness of both agents in preventing bacterial infection. Folia Medica Indonesiana 105

5 Table 6. Distribution of mononuclear (MN) cells count Before After Groups < 5 >=5 Total < 5 >= 5 Total Povidone- iodine 73 (98.6%) 1 (1.4%) 0 ( 0%) 72 (97.3%) 2 (2.7%) 72 (100%) 72 (97.3%) 2 (2.7%) 74 (1oo%) Total 145 (98.0%) 3 (2.0%) 148 (100%) 146 (98.6%) 2 (1.4%) 148 (100%) Laboratory test on the number of MN cells showed that before treatment the number of MN cells of povidoneiodine group had the highest value of 73 babies (98.6%) with MN cell count < 5 per visual field to 74 babies (100%) after treatment. group had 72 babies (97.3%) before treatment to 72 babies (97.3%) with MN cell count < 5 after treatment. Referring to the literature, the higher number of MN cells (> 5 per visual field) serves as parameter indicating the presence of viral infection. In this study, most babies in both groups showed MN cells < 5 per visual field. This indicated that most of the babies were not infected by virus, before and after treatment. Chi-square test showed that p = before treatment after treatment. To conclude, there was no significant difference in the distribution of MN cell count between povidone-iodine group and tetracycline group before and after treatment. Table 7. Bacterial distribution test Before After Group None Bar Coccus Total None Bar Coccus Total Povidone- iodine 38 (51.4%) 26 (35.1%) 10 (13.5%) 69 (93.2%) 4 (5.4%) 1 (1.4%) 36 (48.6%) 20 (27.0%) 18 (24.3%) 65 (87.8%) 3 (4.1%) 6 (8.1%) Total 46 (31.1%) 28 (18.9%) 148 (100%) 134 (90.5%) 7 (4.7%) 7 (4.7%) 148 (100%) Table 7 showed that the bacterial distribution test in the povidone-iodine group revealed 26 babies (35.1%) with bar of gram-negative bacteria before treatment to 4 babies (5.4 %) after treatment. Then, there were 10 babies (13.5%) with gram-positive coccus before treatment and 1 baby (5.4%) after treatment. In the tetracycline group there were 30 babies (27.0%) with bar of gram-negative bacteria before treatment, and decreased to only 3 babies (4.1%) after treatment, while 18 babies (24.3%) with gram-positive coccus decreased to 6 babies (8.1%) after treatment. The decrease of MN cell count using McNemar test showed that p = in each group. Comparing the both groups by chi-square test, the p value was before treatment and after treatment. In conclusion, the effectiveness of povidone-iodine group and tetracycline group were the same in bacterial killing. Referring to the literature, both agents are effective to bust the gram negative and coccus bacteria. CONCLUSIONS AND SUGGESTIONS Conclusions 1. Clinical Test: There were no significant difference between povidone-iodine group and tetracycline group after treatment in edema palpebrae, conjunctive hyperaemia and conjunctive secretion. 2. Laboratory Test: There were no significant difference between povidone-iodine group and tetracycline group after treatment on the distribution of PMN, MN cell count and bacteria. 3. Concerning the result of the clinical and laboratory tests before and after treatment, both agents had the same effectiveness. Suggestion As 2.5% povidone-iodine eye drop and 1% tetracycline eye ointment have the same effectiveness, more cost- Folia Medica Indonesiana 106

6 saving 2.5% povidone-iodine eye drops should be considered to be used as alternative to 1% tetracycline eye ointment to prevent ophthalmia neonatorum, especially that is caused by bacteria. REFERENCES British Columbia Reproductive Care Program, Eye Care and Prevention of Ophthalmia Neonatorum Newborn Guideline 11 Canadian Medical Association Journal Prophylaxis for gonococcal and chlamydial ophthalmia neonatourm, no. 147, pp Diamant IJ and Hwang GD, Ocular infection: Update on therapy. Therapy for Bacterial Conjungtivitis. Opthalmology Clinics of North America. Friendly SD, Ophthalmia Neonatorum : Pediatric Clinics Of North America, Vol. 30, George Washington University, Washington DC, p: Havener WH, Ocular Pharmacology:, CV Mosby Company, St. Louis, Toronto, p : Ho KN, Perinatal infections - Problem of Developing Countries, Singapore Medical Journal (SMJ) Isenberg JS et al, The influences of perinatal infective factors on ophthalmia neonatorum. Jules Stein Eye Institute, UCLA Los Angeles, Kikuyu Eye Hospital, Kikuyu Kenya. Isenberg JS, Ophthalmia Neonatorum : New Techniques to prevent blindness in newborn babies. Pediatric Ophthalmology and Strabismus Division, UCLA School of Medicine, p : Kansky JJ, Clinical Ophthalmology Disorders of the Conjunctiva Neonatal Chlamydial Conjunctivities, Oxford., 4th Edition, p : Kuo Sheree MD, Neonatal Conjungtivitis and Eye Prophylaxis, Chapter XVII. 1 Dept. of Pediatrics, University of Hawaii John A. Burns School of Medicine. Pratiknya WA, Dasar - dasar metodologi penelitian kedokteran dan kesehatan. STD Guidelines US Centers for Disease Control and Prevention, Ophthalmia Neonatorum Prophylaxis. The Journal of American Medical Association, Ophthalmia Neonatorum Prophylaxis. Vaughan GD et al, General Ophthalmology Preventive Ophthalmology, Neonatal Conjunctivitis. University of California, USA, 14th Edition, p: 383 Wilhelmus KR et al External Disease and Cornea: Bacterial Conjungtivitis in Neonatus. Basic and clinical science course, section 8. American Academy of Ophthalmology, San Francisco, pp Wilson MW et al Basic and Clinical Science Course Pediatric Ophthalmology and Strabismus: Ophthalmia Neonatorum, Diagnosis, and Prevention. American Academy of Ophthalmology, USA, pp Zhao Eng MD et al Conjungtivitis, Neonatal, e- Medicine. Staf Dept. Ophthalmology Emory Cartersville Medical Center. Folia Medica Indonesiana 107